Recently, Andrew E. Teschendorff's research group of the Chinese Academy of Sciences Shanghai Institute of Nutrition and Health published a research paper entitled Quantifying the Stochastic component of epigenetic aging on Nature Aging. This study demonstrated that an important component of the epigenetic clock comes from the biological mechanisms that induce random DNA methylation changes. It was found that the more accurate the epigenetic clock is in predicting actual age, the greater the potential random components of the clock. On the contrary, epigenetic clocks perform better in predicting physiological age and have stronger non random components. This reflects that the process of increasing or decreasing physiological age is essentially non random, while the routine pointer movement of epigenetic clocks is determined by the inherent random process of increased DNA methylation changes.

Previously, researchers observed epigenetic covalent modifications of DNA, namely DNA methylation. Changes with age are largely independent of cell and tissue types. Subsequently, epigenetic DNA methylation clocks were developed. Based on the DNA samples of the subjects, the epigenetic clock can accurately predict their actual age and to some extent, predict their physiological age. The epigenetic clock has been proven to be applicable to any mammalian species and has been used to test the efficacy of anti-aging and cell regeneration strategies, as well as other application scenarios. However, in addition to the epigenetic mitotic clock, the potential biological mechanisms of these clocks need to be explored.

Research has found that the average net effect of random DNA methylation changes in cell populations is a linear variation of cumulative DNA methylation changes. On the contrary, biological processes accelerated by age are essentially non random. Previously, scientists believed that accelerated physiological age may only reflect an increase in random DNA methylation changes, while laboratory data suggests otherwise. The only exception to this rule demonstrated in this work is the epigenetic mitotic clock. In cancer or precancerous lesions, the acceleration of mitotic age is reflected in the growth rate of random DNA methylation changes, indicating that DNA methylation changes related to cell division are essentially random.

The research work was supported by the National Natural Science Foundation of China and the Chinese Academy of Sciences.

Paper link



The Institute of Nutrition and Health elucidates the essence of epigenetic clock by quantifying the random components of epigenetic clock